Apparatus for concentrating drugs



Sept. 23, 1947. y c. N. HoYLl-:R 2,427,786

APPARATUS FOR CONCENTRATING DRUGS Filed oct. s, 1944 @P7/gg, y [APatented Sept. 23, 1947 UNITED STATE 2,427,786 APPARATUS FORCONCENTRATING DRUGS cyril N. noyier, Princeton, N. J., assigner to RadioCorporation of America, a corporation ot Delaware Application October 3,1944, Serial No. 557,054

2 Claims. 1

This invention relates to improvements in the art of concentrating ordesiccating drug solutions and other fluent matter o f the type whicheiervesce when subjected to heat and to a vacuum.

The iinal step in the manufacture of the rare drug penicillin consistsin dehydrating or desiccating the preconcentrated liquor in which theX-iactor or active ingredient" of the drug ls contained. Usually, anether extraction process is employed in pre-concentrating the motherliquor and, as a. result, the concentrated liquor may boil with almostexplosive violence if an attempt is made to dehydrate it in an ordinarystili The highly ebullient nature of pre-concentrated penicillin liquorhad led to the use of so-called freeze drying" in preparing the drug formarket. This method (see U. S. Patents 994,555 and Reissue 20,969)obviates losses due to effervescence and has the further advantage ofproviding a zo readily dissoluble sponge-like or a pulverulent product.However, freeze-drying is extremely costly, not only because of theexpensive nature of the high-vacuum apparatus which is necessarilyemployed in practicing this prior art method but because the sublimationof even a few cubic centimeters of the frozen liquor may take severalhours on the pump.

A much more rapid and economical method and apparatus for desiccatingebullient drug liquors in dosage quantities" is described in copendingapplication of Rudolph A. Bierwirth, Serial No. 557,053, led October 3,1944. Bierwirth subjects the bottles or ampoules in 'which the liquor iscontained to an electric ileld, applied in vacuo, while rotatingthebottles so rapidly that the centrifugal force applied to the materialprevents the release of bubbles or other liquid emanations therefrom.The disadvantage (if such it be) of Bierwirths method is that theultimate product comprises neither a powder nor a sponge-like mass but adry film or deposit upon the inner walls of the container. While thedrug in this form is no less potent and no less soluble than it is whenin the form of a powder or spongelike mass, a casual inspection of 4oneof Bierwirths bottles might, in some cases, lead the uninitiatedtobelleve it to be empty.

Accordingly, the principal object of the present invention is to providea rapid and economical method of dehydratng or desiccating penicillinliquor and other ebullient matter, and one which in its practiceprovides a readily soluble cellular or honey-combed product. I

Another and important object of the present in- (Cl. 159-3l) vention isto provide an improved "ampouledrier, and one characterized by thesimplicity and economy of its parts and .by its trouble-freeperformance.

The foregoing and other objects are-achieved in accordance with themethod of the invention lient material, to heat and to a degreel ofvacuum sufllciently high to cause the material to efferverse and then,uum, directing a fine stream of air upon the bubbles or foam in order tobreak-up thesaid liquid emanations and to prevent them l'from beingdrawn oil with the gaseous emanations or vapor. The invention may alsobe said to reside in the provision of a novel and simple form ofapparatus, shown in the accompanying drawing. for carrying the abovedescribed principle into practical commercial use.

The single figure is an elevated side view, shown in section, oi theapparatus used to carry out the pIOcess.

The embodiment of the invention which has been selected for illustrationcomprises a metal 25 platform or base I and a bell jar 3 of specialconstruction which is shown supported on a vacuum tight gasket on thesaid base. 'Ihe space 1 within the bell jar 3 is evacuated through aport 8, in the metal base I, and is connected to a suitable vacuum pump(not shown) through a water cooled condenser Il. The ampoules or bottlesI3 which contain the penicillin liquor or other ebullient liquid I5 aresupported in an upright position preferably in circular array, withinthe evacuable chamber 1 by means of a multiplicity of pairs ofspaced-apart electrodes I1 and I9, re-` spectively. One electrode ofeach pair, say the electrodes I1, is grounded to the metal base I andthe other electrodes, I9, are electrically connected through a commonlead 2 I, which extends through an insulating bushing 23 in the base I,to a source of radio 'frequency energy, exemplified -by the concentrictransmission line 25.

The electric field which is established between the electrodes I1 and I9of each pair serves to heat the contents of the ampoule or bottle I3which is supported there-between, The said liquid foams when subjectedto a vacuum and the foaming is augmented when the liquid is heated.

As previously set forth the inflated liquid iilms or bubbles whichemanate from the liquid are conilned within the ampoules or bottles I3and are then broken-up by directing a fine stream of air upon thefoaming liquid through the open top of each bott1e. To this end, thelbell jar 3 is proby subjecting the penicillin liquor, or otherebulwhile maintaining the vacvided. preferably near its top, with avalved port y 21 through which air may be drawn with considerable forcewhen the chamber 1 is on the pump. A flexible hose 29 extends from theport 21 to a small plenum chamber or distributor" 3l. The part 3| issupported for movement in a vertical direction on a rod33 which has aslideable fit in an air-tight bushing 35 within the handle or knob 31 atthe top of the bell jar 3.

The air or other gas which enters the plenum chamber 3| through the port21 and hose 29 is distributed among the\several bottles I3 through rigidor semirlgid pipes 33., `These pipes 33 depend from the base of thedistributor chambery 3l and are arranged each in register with the opentop of one of the bottles I3, hence the free-end of each pipe 39 isadapted to be inserted in, or withdrawn from, its bottle as determinedby the direction in which the rod or plunger 33 is moved. Each pipe 33may be provided, adjacent to its free end, with an inverted cup-shapeshield 4| to prevent bacteria or other foreign matter from dropping intothe bottles while they are in the vacuum chamber.

In applying the method of the present invention to the desiccation ofpenicillin liquor each of the bott1esl3 had a capacity of about 20cubicv centimeters of liquid and each was provided with a partialiilling of about 1 cubic centimeter. (The liquor had beenpre-concentrated in the lapparatus disclosed in copending applicationSerial No. 536,491 to George H. Brown and the instant applicant, and hada concentration of approximately 100,000 Oxford units per c. c.) Theelectrical energy employed in heating the liquor was supplied by a 0.75kilowatt oscillator operating at a frequency of 150 megacycles persecond and the vacuum pump was adjusted to maintain a vacuum in the mainchamber 1 of the order of from 40 to '70 millimeters of mercury when theport 21 was opened to admit a ne blast of air into the several bottles.The pipes 39 through which the air passed each had an inside diameter ofabout ik of an inch with a hole at the end of a diameter of about 0.003inch. The drying time was approximately 3 minutes in the R. F. field,y

and 5'1 minutes in a vacuum of 10 mm. with 65 F. on the electrodes.prised a potent and readily soluble cellular or "honey-combed masshaving an'appearance similar to that of dry soap-bubbles or froth Whilethe invention lhas been described as applied to the desiccation ofpenicillin liquor it will be apparent that the disclosure in thisrespect is illustrative and should not be interpreted in a limitingsense except as required by the prior art and by the spirit oftheappended claims.

The dried product com` What is claimed is:

1. Apparatus for treating fluent materials of the type which eiIervescewhen subjected to a vacuum, said apparatus comprising an evacuablechamber, means for supporting an open-topped container for said fluentmaterial within said chamber, said supporting means for said containercomprising a plurality of spaced-apart electrodes through which anelectric field may be applied to said container for the purpose ofheating the contents thereof, a port in a wall of said chamber throughwhich air may be drawn when said chamber is evacuated, and meansconnected to said port and adapted t'o be entered into said containerthrough the open top thereof for directing said air in a fine streamupon the surface of said eifervescent material whereby to control theeffervescent condition of said material.

2. Apparatus for treating fluent materials ofI the type which effervescewhen subjected to a vacuum, said apparatus comprising an evacuablechamber, means for supporting a plurality of open-topped containers forsaid fluent material in spaced array within said chamber, a port in awall of said chamber through which air may be drawn when said chamber isevacuated, a plenum chamber mounted for movement within said evacuablechamber, a flexible connection for said air between said'port and saidplenum chamber. a plurality of spaced-apart pipes individual to saidcontainers connected to said plenum chamber and leach having a free-endadapted to be entered into one of said containers through the open-topthereof for directing said air in a fine stream upon the surface of saideffervescent material whereby to control the effervescent condition ofsaid material, and means extending to the exterior of said evacuablechamber for moving said plurality of pipes into and out of saidopentopped containers.

CYRIL N. HOYLER..

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS

